This is a request for renewal of a Program on the neuroanatomical basis of cognition and behavior initiated in 1983, and renewed in 1986, 1991, 1996, and 2001. From the outset, the purposes of the Program have been: (1) to contribute to the understanding, diagnosis, and management of brain disease;(2) to elucidate, in hypothesis-driven research, the relation between large-scale human neural systems and functions such as emotion, decision-making, memory, and language;and (3) to maintain and expand a neurological Patient Registry, which constitutes a unique resource for cognitive neuroscience. The research relies on neurological lesions used as probes to test hypotheses regarding the role of cortical and subcortical systems involved in complex functions. The lesions are defined by in vivo neuroimaging techniques, and the functional impairments are characterized by neuropsychological and psychophysiological techniques. The approach is now strengthened by studies aimed at elucidating the pattern of interconnecting pathways in neural systems, and by the development of powerful new imaging and lesion analysis tools. The investigators have obtained results that have influenced cognitive neuroscience, and have provided a body of knowledge applicable to diagnostic procedures and valuable to inform the design of rehabilitation approaches. The renewal of this Program is likely to yield results of scientific merit and practical importance, potentially even stronger than in the past. The new proposal identifies exciting new questions to pursue, in lesion analysis, neuroeconomics, emotional and social development, social emotions, and memory and language disorders;it demonstrates the stability and cohesiveness of the senior research team, combined with the addition of a performance environment which will strengthen the intellectual and technical resources;and it maintains and expands the highly valuable resource of the Patient Registry. These factors join to provide ideal and compelling circumstances for continuation of the Program. Public health relevance: This research will provide information critical for the diagnosis and treatment of neurological patients who suffer stroke, head injury, brain tumors, seizure disorders, and other brain diseases. The information will help with the design of rehabilitation programs that can alleviate deficits in memory, language, and emotions, and help curb the suffering associated with brain disease.